Water → Isopropyl 4-amino-5,6-difluoropicolinate

HRID 541039Notes

Reaction equation

HRID 541039 reaction equation
F[C:2]1[C:7]([F:8])=[C:6]([F:9])[N:5]=[C:4]([C:10]([O:12][CH:13]([CH3:15])[CH3:14])=[O:11])[CH:3]=1.[OH-].[NH4+:17].O>CN1C(=O)CCC1>[NH2:17][C:2]1[C:7]([F:8])=[C:6]([F:9])[N:5]=[C:4]([C:10]([O:12][CH:13]([CH3:15])[CH3:14])=[O:11])[CH:3]=1

Participants

5

Reactant 3

HCID 962WaterHCID 14923Ammonium HydroxideHCID 70495789Isopropyl 4,5,6-trifluoropicolinate

Product 1

HCID 70496176Isopropyl 4-amino-5,6-difluoropicolinateYield 68%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

Isopropyl 4,5,6-trifluoropicolinate (17.52 g, 80 mmol) was dissolved in NMP (175 g) in a 500 mL flask equipped with a stirring bar. The mixture was blanketed with nitrogen and then ammonium hydroxide (10.70 g 176 mmol, 28% in water) was added to the flask dropwise at room temperature, and the reaction was stirred overnight. To the reaction was added water (190 mL) and the resulting slurry was cooled in an ice bath and stirred for 5 hours. The solid was collected by filtration and the cake washed with water. Vacuum drying provided the isopropyl 4-amino-5,6-difluoropicolinate as an off-white solid (11.7 g, 68% yield, 96% HPLC purity): mp 167-168° C.; 1H NMR (THF-d8, 300 MHz) δ 7.25 (d, 1H, J=6 Hz), 6.07 (s, 2H), 5.01 (m, 1H, J=6 Hz), 1.20 (d, 6H, J=6.3 Hz); 13C NMR (THF-d8, 75 MHz, 1H decoupled) δ 162.9 (s), 151.5 (dd, J=228 Hz, 12 Hz), 146.1 (dd, J=9 Hz, 6 Hz), 140.4 (dd, J=17 Hz, 5 Hz), 134.5 (dd, J=251 Hz, 32 Hz), 111.9 (m), 68.4 (s), 21.0 (s).

Workup

  1. customequipped with a stirring bar
  2. temperaturethe resulting slurry was cooled in an ice bath
  3. stirringstirred for 5 hours
  4. filtrationThe solid was collected by filtration
  5. washthe cake washed with water
  6. customVacuum drying

Sources & evidence

ORD record
ord-be731415eaba41b0bd28e8076f90d388
Source dataset
uspto-grants-2014_10
Patent number
US08871943B2

Reaction notes

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